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Lavender CD, Schaver AL, Taylor S, Peluso R, Berdis G, Singh V, Cipriani K, Lycans D, Jasko J, Hewett TE. Anterior Cruciate Ligament Reconstruction Augmentation With Bone Marrow Aspirate Concentrate, Demineralized Bone Matrix, and Suture Tape Shows No Difference in Outcomes-But Faster Functional Recovery-Versus Non-augmented Anterior Cruciate Ligament Reconstruction. Arthroscopy 2025; 41:1496-1508. [PMID: 39047990 DOI: 10.1016/j.arthro.2024.06.042] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/26/2023] [Revised: 06/14/2024] [Accepted: 06/27/2024] [Indexed: 07/27/2024]
Abstract
PURPOSE To compare outcomes after anterior cruciate ligament reconstruction (ACLR) with bone marrow aspirate concentrate (BMAC), demineralized bone matrix (DBM), and suture tape augmentation (STA) versus ACLR without biological augmentation or STA. METHODS We performed a prospective randomized controlled trial at a single institution to compare ACLR with BMAC, DBM, and STA (group A) versus ACLR without biological augmentation or STA (group NA). The study sought to include 100 patients. Skeletally mature patients younger than 25 years received quadriceps tendon autograft, whereas patients aged 25 years or older underwent allograft ACLR with an all-inside technique. Patients with concomitant meniscal pathologies were included. The primary outcomes compared were range of motion (ROM), limb symmetry, and patient-reported outcomes. Secondary outcomes included radiographic outcomes and surgical complications. Univariate and mixed-model regression analyses were used to compare outcomes. RESULTS Fifty-nine patients were included (29 patients in group A [11 female patients, 38%] and 30 patients in group NA [15 female patients, 50%]). Early ROM at 6 weeks (125° of flexion vs 109° of flexion, P < .0001) and limb symmetry at 12 weeks (80.6% vs 36.7% [delta, 43.9%], P < .001) were significantly improved in group A. At 2 years, International Knee Documentation Committee scores were similar (91.1 ± 12.7 vs 85.3 ± 10.8, P = .109). Quality-of-life subscores of the Knee Injury and Osteoarthritis Outcome Score were significantly enhanced in group A (85.2 ± 20.9 vs 72.1 ± 20.4, P = .042). In 22 patients (12 in group A and 10 in group NA), computed tomography scans were obtained at 6 months to compare bone tunnel healing. Overall, the mean increase in bone tunnel diameter was significantly smaller in group A than in group NA. No difference in graft rerupture or reoperation rate was observed. Reoperations were performed for stiffness in 7 of 59 patients (11.9%) (3 [10%] in group A vs 4 [13%] in group NA; P > .999). CONCLUSIONS There were no differences in International Knee Documentation Committee scores between groups at 2-year follow-up. Functional outcomes including early ROM and limb symmetry were significantly improved in patients who received ACLR with BMAC, DBM, and STA. LEVEL OF EVIDENCE Level II, randomized controlled trial.
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Affiliation(s)
- Chad D Lavender
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A..
| | - Andrew L Schaver
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Shane Taylor
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Richard Peluso
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Galen Berdis
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Vishapreet Singh
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Kara Cipriani
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Dana Lycans
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - John Jasko
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
| | - Timothy E Hewett
- Department of Orthopedic Surgery, Marshall University, Huntington, West Virginia, U.S.A
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Yao S, Yung PSH, Lui PPY. Tackling the Challenges of Graft Healing After Anterior Cruciate Ligament Reconstruction-Thinking From the Endpoint. Front Bioeng Biotechnol 2022; 9:756930. [PMID: 35004636 PMCID: PMC8727521 DOI: 10.3389/fbioe.2021.756930] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2021] [Accepted: 11/09/2021] [Indexed: 12/30/2022] Open
Abstract
Anterior cruciate ligament (ACL) tear is common in sports and accidents, and accounts for over 50% of all knee injuries. ACL reconstruction (ACLR) is commonly indicated to restore the knee stability, prevent anterior–posterior translation, and reduce the risk of developing post-traumatic osteoarthritis. However, the outcome of biological graft healing is not satisfactory with graft failure after ACLR. Tendon graft-to-bone tunnel healing and graft mid-substance remodeling are two key challenges of biological graft healing after ACLR. Mounting evidence supports excessive inflammation due to ACL injury and ACLR, and tendon graft-to-bone tunnel motion negatively influences these two key processes. To tackle the problem of biological graft healing, we believe that an inductive approach should be adopted, starting from the endpoint that we expected after ACLR, even though the results may not be achievable at present, followed by developing clinically practical strategies to achieve this ultimate goal. We believe that mineralization of tunnel graft and ligamentization of graft mid-substance to restore the ultrastructure and anatomy of the original ACL are the ultimate targets of ACLR. Hence, strategies that are osteoinductive, angiogenic, or anti-inflammatory should drive graft healing toward the targets. This paper reviews pre-clinical and clinical literature supporting this claim and the role of inflammation in negatively influencing graft healing. The practical considerations when developing a biological therapy to promote ACLR for future clinical translation are also discussed.
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Affiliation(s)
- Shiyi Yao
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Patrick Shu Hang Yung
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
| | - Pauline Po Yee Lui
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China
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Matsumoto T, Sato Y, Kobayashi T, Suzuki K, Kimura A, Soma T, Ito E, Kikuchi T, Kobayashi S, Harato K, Niki Y, Matsumoto M, Nakamura M, Miyamoto T. Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction. Am J Sports Med 2021; 49:3508-3518. [PMID: 34643475 DOI: 10.1177/03635465211041582] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
BACKGROUND Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). HYPOTHESIS ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. STUDY DESIGN Controlled laboratory study. METHODS A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro-computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. RESULTS The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 (P = .01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 (P = .003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 (P = .59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 (P = .24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 (P = .39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro-computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. CONCLUSION ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. CLINICAL RELEVANCE ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR.
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Affiliation(s)
- Tatsuaki Matsumoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yuiko Sato
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Tami Kobayashi
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Kunika Suzuki
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Regenerative Medicine iPS Gateway Center, Tokyo, Japan
| | - Atsushi Kimura
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Tomoya Soma
- Division of Oral and Maxillofacial Surgery, Department of Dentistry and Oral Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Eri Ito
- Institute for Integrated Sports Medicine, School of Medicine, Keio University, Tokyo, Japan
| | - Toshiyuki Kikuchi
- Department of Clinical Research, National Hospital Organization Murayama Medical Center, Tokyo, Japan
| | - Shu Kobayashi
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Kengo Harato
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Yasuo Niki
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Morio Matsumoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Masaya Nakamura
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan
| | - Takeshi Miyamoto
- Department of Orthopedic Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Advanced Therapy for Musculoskeletal Disorders II, School of Medicine, Keio University, Tokyo, Japan; Department of Musculoskeletal Reconstruction and Regeneration Surgery, School of Medicine, Keio University, Tokyo, Japan; Department of Orthopedic Surgery, Kumamoto University, Kumamoto, Japan
- Investigation performed at Keio University, Tokyo, Japan
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Taguchi T, Zhang N, Angibeau D, Spivey KP, Lopez MJ. Evaluation of canine adipose-derived multipotent stromal cell differentiation to ligamentoblasts on tensioned collagen type I templates in a custom bioreactor culture system. Am J Vet Res 2021; 82:924-934. [PMID: 34669492 DOI: 10.2460/ajvr.82.11.924] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
Abstract
OBJECTIVE To evaluate differentiation of canine adipose-derived multipotent stromal cells (ASCs) into ligamentoblasts on tensioned collagen type I (Col1) templates in a perfusion culture system. SAMPLES Infrapatellar fat pad ASCs from healthy stifle joints of 6 female mixed-breed dogs. PROCEDURES Third-passage ASCs (6 × 106 cells/template) were loaded onto suture-augmented Col1 templates under 15% static strain in perfusion bioreactors. Forty-eight ASC-Col1 constructs were incubated with ligamentogenic (ligamentogenic constructs; n = 24) or stromal medium (stromal constructs; 24) for up to 21 days. Specimens were collected from each construct after 2 hours (day 0) and 7, 14, and 21 days of culture. Cell number, viability, distribution, and morphology; construct collagen content; culture medium procollagen-I-N-terminal peptide concentration; and gene expression were compared between ligamentogenic and stromal constructs. RESULTS ASCs adhered to collagen fibers. Cell numbers increased from days 0 to 7 and days 14 to 21 for both construct types. Relative to stromal constructs, cell morphology and extracellular matrix were more mature and collagen content on day 21 and procollagen-I-N-terminal peptide concentration on days 7 and 21 were greater for ligamentogenic constructs. Ligamentogenic constructs had increased expression of the genes biglycan on day 7, decorin throughout the culture period, and Col1, tenomodulin, fibronectin, and tenascin-c on day 21; expression of Col1, tenomodulin, and tenascin-c increased between days 7 and 21. CONCLUSIONS AND CLINICAL RELEVANCE Ligamentogenic medium was superior to stromal medium for differentiation of ASCs to ligamentoblasts on suture-augmented Col1 scaffolds. Customized ligament neotissue may augment treatment options for dogs with cranial cruciate ligament rupture.
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Affiliation(s)
- Takashi Taguchi
- From the Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
| | - Nan Zhang
- From the Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
| | - Dominique Angibeau
- From the Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
| | - Kathryn P Spivey
- From the Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
| | - Mandi J Lopez
- From the Laboratory for Equine and Comparative Orthopedic Research, Department of Veterinary Clinical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803
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Hexter AT, Karali A, Kao A, Tozzi G, Heidari N, Petrie A, Boyd A, Kalaskar DM, Pendegrass C, Rodeo S, Haddad F, Blunn G. Effect of Demineralized Bone Matrix, Bone Marrow Mesenchymal Stromal Cells, and Platelet-Rich Plasma on Bone Tunnel Healing After Anterior Cruciate Ligament Reconstruction: A Comparative Micro-Computed Tomography Study in a Tendon Allograft Sheep Model. Orthop J Sports Med 2021; 9:23259671211034166. [PMID: 34568508 PMCID: PMC8461134 DOI: 10.1177/23259671211034166] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2021] [Accepted: 04/29/2021] [Indexed: 12/02/2022] Open
Abstract
Background: The effect of demineralized bone matrix (DBM), bone marrow–derived mesenchymal stromal cells (BMSCs), and platelet-rich plasma (PRP) on bone tunnel healing in anterior cruciate ligament reconstruction (ACLR) has not been comparatively assessed. Hypothesis: These orthobiologics would reduce tunnel widening, and the effects on tunnel diameter would be correlated with tunnel wall sclerosis. Study Design: Controlled laboratory study. Methods: A total of 20 sheep underwent unilateral ACLR using tendon allograft and outside-in interference screw fixation. The animals were randomized into 4 groups (n = 5 per group): Group 1 received 4mL of DBM paste, group 2 received 10 million BMSCs in fibrin sealant, group 3 received 12 mL of activated leukocyte-poor platelet-rich plasma, and group 4 (control) received no treatment. The sheep were euthanized after 12 weeks, and micro-computed tomography scans were performed. The femoral and tibial tunnels were divided into thirds (aperture, midportion, and exit), and the trabecular bone structure, bone mineral density (BMD), and tunnel diameter were measured. Tunnel sclerosis was defined by a higher bone volume in a 250-µm volume of interest compared with a 4-mm volume of interest surrounding the tunnel. Results: Compared with the controls, the DBM group had a significantly higher bone volume fraction (bone volume/total volume [BV/TV]) (52.7% vs 31.8%; P = .020) and BMD (0.55 vs 0.47 g/cm3; P = .008) at the femoral aperture and significantly higher BV/TV at femoral midportion (44.2% vs 32.9%; P = .038). There were no significant differences between the PRP and BMSC groups versus controls in terms of trabecular bone analysis or BMD. In the controls, widening at the femoral tunnel aperture was significantly greater than at the midportion (46.7 vs 41.7 mm2; P = .034). Sclerosis of the tunnel was common and most often seen at the femoral aperture. In the midportion of the femoral tunnel, BV/TV (r = 0.52; P = .019) and trabecular number (rS = 0.50; P = .024) were positively correlated with tunnel widening. Conclusion: Only DBM led to a significant increase in bone volume, which was seen in the femoral tunnel aperture and midportion. No treatment significantly reduced bone tunnel widening. Tunnel sclerosis in the femoral tunnel midportion was correlated significantly with tunnel widening. Clinical Relevance: DBM might have potential clinical use to enhance healing in the femoral tunnel after ACLR.
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Affiliation(s)
- Adam T Hexter
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Aikaterina Karali
- Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, UK
| | - Alex Kao
- Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, UK
| | - Gianluca Tozzi
- Zeiss Global Centre, School of Mechanical and Design Engineering, University of Portsmouth, Portsmouth, UK
| | - Nima Heidari
- Royal London Hospital and Orthopaedic Specialists (OS), London, UK
| | - Aviva Petrie
- Eastman Dental Institute, University College London, London, UK
| | - Ashleigh Boyd
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Deepak M Kalaskar
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Catherine Pendegrass
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Scott Rodeo
- Hospital of Special Surgery, New York, New York, USA
| | | | - Gordon Blunn
- School of Pharmacy and Biomedical Sciences, University of Portsmouth, Portsmouth, UK
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Application of Stem Cell Therapy for ACL Graft Regeneration. Stem Cells Int 2021; 2021:6641818. [PMID: 34381504 PMCID: PMC8352687 DOI: 10.1155/2021/6641818] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Revised: 02/19/2021] [Accepted: 06/30/2021] [Indexed: 02/07/2023] Open
Abstract
Graft regeneration after anterior cruciate ligament (ACL) reconstruction surgery is a complex three-stage process, which usually takes a long duration and often results in fibrous scar tissue formation that exerts a detrimental impact on the patients' prognosis. Hence, as a regeneration technique, stem cell transplantation has attracted increasing attention. Several different stem cell types have been utilized in animal experiments, and almost all of these have shown good capacity in improving tendon-bone regeneration. Various differentiation inducers have been widely applied together with stem cells to enhance specific lineage differentiation, such as recombinant gene transfection, growth factors, and biomaterials. Among the various different types of stem cells, bone marrow-derived mesenchymal stem cells (BMSCs) have been investigated the most, while ligament stem progenitor cells (LDSCs) have demonstrated the best potential in generating tendon/ligament lineage cells. In the clinic, 4 relevant completed trials have been reported, but only one trial with BMSCs showed improved outcomes, while 5 relevant trials are still in progress. This review describes the process of ACL graft regeneration after implantation and summarizes the current application of stem cells from bench to bedside, as well as discusses future perspectives in this field.
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Xu Y, Zhang WX, Wang LN, Ming YQ, Li YL, Ni GX. Stem cell therapies in tendon-bone healing. World J Stem Cells 2021; 13:753-775. [PMID: 34367476 PMCID: PMC8316867 DOI: 10.4252/wjsc.v13.i7.753] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 05/08/2021] [Accepted: 06/23/2021] [Indexed: 02/06/2023] Open
Abstract
Tendon-bone insertion injuries such as rotator cuff and anterior cruciate ligament injuries are currently highly common and severe. The key method of treating this kind of injury is the reconstruction operation. The success of this reconstructive process depends on the ability of the graft to incorporate into the bone. Recently, there has been substantial discussion about how to enhance the integration of tendon and bone through biological methods. Stem cells like bone marrow mesenchymal stem cells (MSCs), tendon stem/progenitor cells, synovium-derived MSCs, adipose-derived stem cells, or periosteum-derived periosteal stem cells can self-regenerate and potentially differentiate into different cell types, which have been widely used in tissue repair and regeneration. Thus, we concentrate in this review on the current circumstances of tendon-bone healing using stem cell therapy.
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Affiliation(s)
- Yue Xu
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Wan-Xia Zhang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Li-Na Wang
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yue-Qing Ming
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Yu-Lin Li
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China
| | - Guo-Xin Ni
- School of Sports Medicine and Rehabilitation, Beijing Sport University, Beijing 100084, China.
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Yao S, Fu BSC, Yung PSH. Graft healing after anterior cruciate ligament reconstruction (ACLR). ASIA-PACIFIC JOURNAL OF SPORT MEDICINE ARTHROSCOPY REHABILITATION AND TECHNOLOGY 2021; 25:8-15. [PMID: 34094881 PMCID: PMC8134949 DOI: 10.1016/j.asmart.2021.03.003] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2020] [Revised: 02/05/2021] [Accepted: 03/21/2021] [Indexed: 01/11/2023]
Abstract
Anterior cruciate ligament reconstruction (ACLR) is a commonly performed procedure in Orthopaedic sports medicine. With advances in surgical techniques providing better positioning and fixation of the graft, subsequent graft failure to certain extent should be accounted by poor graft healing. Although different biological modulations for enhancement of graft healing have been tried in different clinical and animal studies, complete graft incorporation into bone tunnels and the “ligamentization” of the intra-articular part have not been fully achieved yet. Based on the understanding of graft healing process and its failure mechanism, the purpose of this review is to combine both the known basic science & clinical evidence, to provide a much clearer picture of the obstacle encountered in graft healing, so as to facilitate researchers on subsequent work on the enhancement of ACL graft healing.
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Affiliation(s)
- Shiyi Yao
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong
| | - Bruma Sai-Chuen Fu
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong
| | - Patrick Shu-Hang Yung
- Department of Orthopaedics and Traumatology, The Chinese University of Hong Kong, Hong Kong
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He X, Li Y, Guo J, Xu J, Zu H, Huang L, Tim-Yun Ong M, Shu-Hang Yung P, Qin L. Biomaterials developed for facilitating healing outcome after anterior cruciate ligament reconstruction: Efficacy, surgical protocols, and assessments using preclinical animal models. Biomaterials 2020; 269:120625. [PMID: 33395579 DOI: 10.1016/j.biomaterials.2020.120625] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2020] [Revised: 12/16/2020] [Accepted: 12/18/2020] [Indexed: 12/17/2022]
Abstract
Anterior cruciate ligament (ACL) reconstruction is the recommended treatment for ACL tear in the American Academy of Orthopaedic Surgeons (AAOS) guideline. However, not a small number of cases failed because of the tunnel bone resorption, unsatisfactory bone-tendon integration, and graft degeneration. The biomaterials developed and designed for improving ACL reconstruction have been investigated for decades. According to the Food and Drug Administration (FDA) and the International Organization for Standardization (ISO) regulations, animal studies should be performed to prove the safety and bioeffect of materials before clinical trials. In this review, we first evaluated available biomaterials that can enhance the healing outcome after ACL reconstruction in animals and then discussed the animal models and assessments for testing applied materials. Furthermore, we identified the relevance and knowledge gaps between animal experimental studies and clinical expectations. Critical analyses and suggestions for future research were also provided to design the animal study connecting basic research and requirements for future clinical translation.
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Affiliation(s)
- Xuan He
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Ye Li
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Jiaxin Guo
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Jiankun Xu
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Haiyue Zu
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Le Huang
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Michael Tim-Yun Ong
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Patrick Shu-Hang Yung
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region
| | - Ling Qin
- Musculoskeletal Research Laboratory of Department of Orthopaedics & Traumatology and Innovative Orthopaedic Biomaterial and Drug Translational Research Laboratory of Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong Special Administrative Region.
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Yue L, DeFroda SF, Sullivan K, Garcia D, Owens BD. Mechanisms of Bone Tunnel Enlargement Following Anterior Cruciate Ligament Reconstruction. JBJS Rev 2020; 8:e0120. [DOI: 10.2106/jbjs.rvw.19.00120] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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